This study used ALFF and DC methods to explore altered intrinsic brain activities in SD and neural mechanism of ICBT efficacy. We found that compared to HC, ALFF in the right INS was increased, while DC in the right PCUN was decreased in SD before ICBT intervention. After ICBT intervention, increased ALFF in the left HIP and decreased DC in the right DCG were found in SD. Furthermore, correlation analyses revealed a negative relationship between altered ALFF values in the left HIP and the changes in PHQ-9 scores, but a positive relationship with the changes in FATS-ReB scores. And altered DC values in the right DCG were positively correlated with the changes in CCTS-TR-BhA scores.
Our research revealed a decrease in DC of the right PCUN in SD compared to HC. The PCUN is an integral component of the DMN, involved in processes such as mentalizing, self-referential thinking, scene construction, and episodic memory subsystem linked to visual-spatial imagery[34, 35]. A previous study has indicated that the PCUN serves as a highly interconnected core hub with high energy demands due to its involvement in cognition and emotion[35]. A rsf-MRI study showed that college students with SD exhibited altered ALFF and regional homogeneity (ReHo) in the right PCUN compared to HC[36]. Li et al. reported increased gray matter volume in the PCUN in Young women with SD[37]. Another study related to MDD revealed widespread disruption in FC networks involving the PCUN, which was associated with the manifestation of depressive symptoms[38].
The INS plays a significant role in attention and working memory, specifically in social judgments, empathy processes, and accurate internal perception[39, 40]. This study found that compared to HC, ALFF in the right INS was increased in SD, consistent with previous research indicating elevated ALFF in the right anterior INS in SD[12]. Additionally, a rs-fMRI study showed abnormal FC between the INS and dorsolateral prefrontal cortex in SD, associating with impaired cognitive control and emotion processing[41]. Philippi et al.'s study reported that decreased FC between the anterior INS and anterior subgenual ACC was correlated with increased severity of depressive symptoms in SD [42].
After ICBT intervention, there was an observed increase in the ALFF in the left HIP of SD. The HIP is essential for modulating mood, cognition, and memory consolidation, and influences behavior in response to emotional or threatening stimuli, displaying heightened sensitivity to stress and negative affect[43, 44]. Individuals exhibiting depressive symptoms were believed to have increased susceptibility to stress, negative stimuli, and subsequent neuro-psychological reactions[45]. Several neuroimaging studies found a significant improvement in hippocampal function following CBT intervention for MDD. A positron emission tomography (PET) study revealed that, CBT resulted in improved clinical symptoms and increased HIP metabolism, whereas paroxetine, a commonly used antidepressant, was associated with decreased HIP metabolism[46]. These findings suggested that distinct therapeutic approaches were employed between CBT and pharmacotherapy in the treatment of MDD. Our findings indicated that increased brain activity in the left HIP underlying ICBT intervention was similar to therapeutic principles of CBT. In addition, a separate task-based functional MRI study showed heightened arousal responses in the HIP of patients with MDD following CBT intervention[47]. These results suggested that ICBT may share similar neurobiological mechanisms with traditional CBT in enhancing hippocampal function, potentially playing a crucial role in the efficacy of ICBT for SD.
The region of the DCG has been identified as a crucial element in higher cognitive functions such as response inhibition[48]. A rs-fMRI investigation showed elevated ALFF in the right DCG of adolescents with MDD who engaged in non-suicidal self-injury[49]. Our present research observed a significant decrease in DC of the right DCG in SD after ICBT intervention. It was hypothesized that SD may undergo a process of improved brain activity in the right DCG after receiving ICBT intervention.
The study revealed that after ICBT intervention, the increase of ALFF in the left HIP was associated with the improvement of depressive symptoms and the frequency of participating in ReB in SD. The findings aligned with prior neuroimaging research suggesting that structural or functional improvements in the HIP may linked to symptom alleviation in depressive symptoms[50, 51], as well as the CBT-related skill[52, 53]. Given that our ICBT was grounded in the fundamental principles of traditional CBT, we hypothesized that, similar to offline CBT, ICBT may increase the utilization of CBT-related skills in individuals with depressive symptoms. Moreover, decreased DC in the right DCG positively correlated with improved BhA skills but not with the depressive/anxiety symptoms. While there is currently a lack of direct evidence linking structural or functional changes in the DCG with BhA skills, our hypothesis posited that SD may influence the brain activity of DCG by enhancing their mastery and usage frequency of BhA skills. Although, the results of mediation analyses showed no statistical significance in this study. These findings suggested potential strategies for enhancing the efficacy of ICBT by increasing the mastery or frequency of ReB and BhA skills.
This study has several limitations. First, although it was a longitudinal study, only one round of MRI scans and psychological assessments were conducted after ICBT intervention, preventing us from tracking long-term effects. Future research should include long-term follow-ups to observe the sustained effects of ICBT and changes in brain structure and function over time. Second, the sample size in this study was relatively small. Although our findings preliminarily identify target brain regions for ICBT efficacy in SD, larger samples are needed for further validation. Lastly, this study lacked an intervention control group, which may limit the accuracy of our findings since we cannot definitively attribute the observed brain region improvements to the ICBT intervention versus natural remission of depressive symptoms. Therefore, future research should incorporate a waitlist control group and an offline CBT group.